title: Preanalytical stringency: what factors may confound interpretation of thiopurine S-methyl transferase enzyme activity?
abstract: BACKGROUND
  Measurement of red blood cell thiopurine S-methyl transferase (TPMT) enzyme activity before commencing thiopurine therapy is recommended to avoid severe bone marrow suppression in TPMT-deficient patients. Patient's samples go through preanalytical transportation and storage steps before measurement. We studied patient's TPMT activity sample data to assess the effect of preanalytical variables including transportation time.
  
  
  METHODS
  A total of 8524 TPMT enzyme activity analyses were conducted from 2002 to 2010 in a single laboratory, with samples sent from seven centres throughout New Zealand. TPMT activity was correlated with time of arrival at the reference laboratory, patient gender and age and centre of sample collection.
  
  
  RESULTS
  The 6348 (74%) selected TPMT measurements that fulfilled selection criteria ranged from 0 to 25.8 IU/mL. Median delay to sample analysis was 42 h. Median TPMT activity was significantly lower for all centres compared with the reference centre (P < 0.001). Delay in sample arrival was significantly and independently correlated with TPMT enzyme activity (ANCOVA; P < 0.001), which showed a 0.011 (95% CI, 0.008-0.014) IU/mL decrease per extra hour of delay. After correcting for these data, one centre still had a significantly lower TPMT enzyme activity compared with the reference centre.
  
  
  CONCLUSIONS
  There was a significant negative correlation between TPMT enzyme activity and delay from sample collection to analysis. Transportation time is therefore an important preanalytical variable influencing TPMT activity. Samples from one centre had a lower TPMT activity after correcting for transportation delay, suggesting that other factors related to sample processing may also be relevant.
authors.affiliation: Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Remco
authors.initials: R
authors.lastname: van Egmond
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
authors.forename: Paul K L
authors.initials: PK
authors.lastname: Chin
authors.forename: Christiaan W
authors.initials: CW
authors.lastname: Sies
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Florkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D057075:Enzyme Assays; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007223:Infant; D008297:Male; D008780:Methyltransferases / Q000097:blood*; D008875:Middle Aged; D009520:New Zealand; D011687:Purines / Q000378:metabolism / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013048:Specimen Handling / Q000592:standards*; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000627:therapeutic use; D014186:Transportation
chemical_list: D011687:Purines; D013438:Sulfhydryl Compounds; D008780:Methyltransferases; C022745:thiopurine methyltransferase
keywords: Enzymes; analytes; clinical studies; laboratory methods; purine metabolism; quality assurance & control